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Baricitinib
Olumiant® (baricitinib) tablets
1mg, 2mg, 4mgbaricitinib
1mg, 2mg, 4mgThis information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.
What are the results from the 36-week placebo-controlled period of the Olumiant® (baricitinib) phase 3 trials in adult patients with severe alopecia areata?
During the 36-week placebo-controlled period of BRAVE-AA1 and BRAVE-AA2, baricitinib was superior to placebo in achieving hair regrowth. Safety results are consistent with baricitinib’s known safety profile. Studies extend up to 200 weeks of treatment.
See important safety information, including boxed warning, in the attached prescribing information.
Content Overview
VIDEO: BRAVE-AA1 and BRAVE-AA2 Phase 3 Results From the 36-Week Placebo-Controlled Period
BRAVE-AA1 and BRAVE-AA2 Study Design Overview
Baseline Demographics and Clinical Characteristics
- Proportion of Patients Achieving SALT ≤20 at Week 36
- Proportion of Patients Achieving Clinician Reported Outcome Measure for Eyebrows and Eyelashes at Week 36
VIDEO: BRAVE-AA1 and BRAVE-AA2 Phase 3 Results From the 36-Week Placebo-Controlled Period
Please click on the video link below for an overview of the BRAVE-AA1 and BRAVE-AA2 phase 3 results from the 36-week placebo-controlled period in patients with severe alopecia areata (AA). Studies extend up to 200 weeks of treatment.1
Abbreviation: AA = alopecia areata.
BRAVE-AA1 and BRAVE-AA2 Study Design Overview
BRAVE-AA1 (NCT03570749) and BRAVE-AA2 (NCT03899259) are multicenter, double-blind, placebo-controlled studies evaluating the efficacy and safety of baricitinib in adult patients with severe alopecia areata (AA).1
BRAVE-AA1 is an adaptive phase 2/3 study and BRAVE-AA2 is a phase 3 study.1
The phase 3 BRAVE-AA1 and BRAVE-AA2 have identical eligibility criteria and identical primary and key secondary outcomes for the 36-week placebo-controlled treatment periods.1 The trials differed after 52 weeks in responding patients where BRAVE-AA1 included a randomized withdrawal substudy, and BRAVE-AA2 had a randomized down-titration substudy.1
BRAVE-AA1 and BRAVE-AA2 Phase 3 Study Design* Through 36 Weeks presents a study design overview of the BRAVE-AA1 and BRAVE-AA2 36-week placebo-controlled period. In both trials, patients were randomized 2:2:3 to receive once-daily oral
- placebo
- baricitinib 2 mg, or
- baricitinib 4 mg.1
A washout of systemic and topical treatments for AA was incorporated before randomization to minimize confounding effects of prior treatment.1,2
Efficacy and safety data during the 36-week placebo-controlled period of BRAVE-AA1 and BRAVE-AA2 will be presented here.
Figure Description: The phase 3 BRAVE-AA1 and BRAVE-AA2 studies included a 36-week double-blinded placebo-controlled period where patients with severe alopecia areata were randomized 2:2:3 to received once-daily oral placebo, baricitinib 2 mg, or baricitinib 4 mg. The primary endpoint of the phase 3 BRAVE-AA studies is the proportion of patients achieving a score of 20 or less on the Severity Alopecia Tool at week 36. This is equivalent to 20% or less scalp hair loss or 80% or more of scalp coverage with hair.
Abbreviations: AA = alopecia areata; BARI = baricitinib; PBO = placebo; QD = once daily; SALT = Severity of Alopecia Tool; W = week.
* This figure does not represent the full study design but only the placebo-controlled period of both trials.
Clinical Assessments
Clinical assessment of AA used in BRAVE-AA1 and BRAVE-AA2 included
- the Severity of Alopecia Tool (SALT) score, representing the extent in percentage of scalp hair loss and ranging from 0 (no hair loss) to 100 (complete hair loss), and
- the Clinician-Reported Outcome (ClinRO) Measures for Eyebrow Hair LossTM and Eyelash Hair LossTM, ranging from a scale of 0 = full eyebrow or eyelash coverage to 3 = no notable eyebrow or eyelash hair.1,3,4
Key Inclusion and Exclusion Criteria
Patients enrolled in BRAVE-AA1 and BRAVE-AA2 had
- severe hair loss encompassing ≥50% of the scalp and measured by SALT score ≥50
- a current episode of AA >6 months to <8 years, and
- no spontaneous improvement (ie, ≤10-point reduction in SALT score) <6 months of screening.1
Patients who had AA for ≥8 years could be enrolled if episodes of regrowth, spontaneous or under treatment, had been observed on the affected areas over the past 8 years.1
In addition, patients were ≥18 to ≤60 (males) or ≤70 (females) years of age with the difference in upper age limit between genders meant to reduce the impact of concomitant androgenetic alopecia on SALT assessment.1
Patients were excluded from BRAVE-AA1 and BRAVE-AA2 if they
- had primarily “diffuse” pattern of AA
- other forms of alopecia, including but not limited to
- primary androgenetic alopecia
- trichotillomania
- telogen effluvium, or
- chemotherapy-induced hair loss, or
- recently received therapies including corticosteroids, other topical therapies, or janus kinase (JAK) inhibitors.1
No concomitant treatments for AA were allowed during the studies with the exceptions of
- oral/topical minoxidil or finasteride if on stable dose for ≥12 months, and
- bimatoprost ophthalmic solution for eyelashes if on stable dose for ≥8 weeks.1
Study Endpoints
The primary endpoint of BRAVE-AA1 and BRAVE-AA2 was the proportion of patients achieving SALT score ≤20 (≤20% scalp hair loss or ≥80% of scalp coverage with hair) at week 36.1
Key secondary endpoints included the proportion of patients achieving at week 36 a score of 0 or 1 with ≥2-point improvement from baseline in the
- ClinRO Measure for Eyebrow Hair Loss, and
- ClinRO Measure for Eyelash Hair Loss.1
For these measures, a score of 0 or 1 indicates full coverage or minimal gaps in eyebrows and eyelashes. Both outcomes were only assessed in patients with a score of ≥2 at baseline, ie having significant gaps or no notable eyebrows or eyelashes.1
In the BRAVE-AA trials, primary and key secondary endpoint analyses were adjusted for multiplicity of statistical comparisons.1
Baseline Demographics and Clinical Characteristics
Patient baseline demographics and clinical characteristics in BRAVE-AA1 and BRAVE-AA2 are presented in Baseline Demographics and Clinical Characteristics in BRAVE-AA1 and BRAVE-AA2.
|
BRAVE-AA1 |
BRAVE-AA2 |
||||
Placebo |
BARI 2 mg |
BARI 4 mg |
Placebo |
BARI 2 mg |
BARI 4 mg |
|
Age, years |
37.4 (12.9) |
38.0 (12.8) |
36.3 (13.3) |
37.1 (12.4) |
39.0 (13.0) |
38.0 (12.7) |
Female, n (%) |
109 (57.7) |
109 (59.2) |
165 (58.7) |
98 (62.8) |
103 (66.0) |
144 (61.5) |
Race, n (%) |
||||||
White |
83 (44.1) |
93 (50.8) |
123 (43.9) |
85 (54.5) |
92 (59.0) |
144 (61.5) |
Asian |
78 (41.5) |
76 (41.5) |
114 (40.7) |
51 (32.7) |
49 (31.4) |
67 (28.6) |
Black |
17 (9.0) |
7 (3.8) |
28 (10.0) |
16 (10.3) |
12 (7.7) |
18 (7.7) |
Other |
10 (5.3) |
7 (3.8) |
15 (5.4) |
4 (2.6) |
3 (1.9) |
5 (2.1) |
BMI, kg/m2 |
26.3 (6.0) |
26.0 (5.4) |
26.4 (5.5) |
26.2 (5.5) |
26.2 (5.1) |
26.4 (4.9) |
Duration of AA since onset, years |
12.6 (11.2) |
12.1 (9.8) |
11.8 (11.1) |
11.8 (10.2) |
13.1 (11.8) |
11.9 (11.1) |
Duration of current AA episode, n (%) |
||||||
<4 years |
134 (70.9) |
127 (69.0) |
189 (67.3) |
94 (60.3) |
103 (66.0) |
140 (59.8) |
≥4 years |
55 (29.1) |
57 (31.0) |
92 (32.7) |
62 (39.7) |
53 (34.0) |
94 (40.2) |
Patients with universalis,a n (%) |
74 (39.2) |
83 (45.1) |
127 (45.2) |
66 (42.3) |
70 (44.9) |
111 (47.4) |
SALT score |
84.7 (17.8) |
86.8 (18.0) |
85.3 (18.2) |
85 (17.8) |
85.6 (18.1) |
84.8 (18.1) |
Severity, n (%) |
||||||
Severe (SALT 50-94) |
92 (48.7) |
77 (41.8) |
133 (47.3) |
74 (47.7) |
70 (44.9) |
115 (49.1) |
Very severe (SALT 95-100) |
97 (51.3) |
107 (58.2) |
148 (52.7) |
81 (52.3) |
86 (55.1) |
119 (50.9) |
ClinRO measures, n (%) |
||||||
Eyebrow hair loss, score of 2 or 3b |
124 (66.3) |
136 (73.9) |
188 (67.6) |
112 (73.2) |
104 (66.7) |
161 (69.1) |
Eyelash hair loss, score of 2 or 3b |
96 (51.3) |
111 (60.3) |
167 (60.1) |
90 (58.8) |
89 (57.1) |
140 (60.1) |
SALT = Severity of Alopecia Tool.
aAs assessed by investigator.
bClinRO and PRO scores of 2 indicate significant gaps in eyebrows/eyelashes and scores of 3 indicate no notable eyebrows/eyelashes.
Efficacy Results
Efficacy analyses included all randomized patients with treatment comparisons analyzed using logistic regression and analysis of covariance (ANCOVA).1
Data were considered missing if patients had
- permanent discontinuation from study treatment or trial, or
- data collected remotely because of the coronavirus disease 2019 (Covid-19) pandemic.1
The efficacy results presented here are based on prespecified analyses in which missing data of categorical endpoints were imputed as nonresponse (published in King et al. 2022 supplemental materials).1
Please refer to the published manuscript for additional analyses using multiple imputation per journal requirements. Due to similarity in outcomes, analyses using multiple imputation are not repeated here.
Proportion of Patients Achieving SALT ≤20 at Week 36
Significantly greater proportions of patients met the primary outcome with baricitinib treatment versus placebo in both trials.1
At week 36 in both BRAVE-AA1 and BRAVE-AA2, significantly more patients treated with baricitinib 4 mg and 2 mg achieved a SALT score ≤20 compared to those receiving placebo (p≤.001 for all; Proportions of Patients Achieving SALT Score ≤20 Through Week 36 in BRAVE-AA1 and BRAVE-AA2).1
Figure Description: At week 36, in both BRAVE-AA1 and BRAVE-AA2, the proportion of patients achieving a score of 20 or less on the Severity Alopecia Tool was significantly higher in the baricitinib 4-mg and 2-mg groups compared to placebo.
A score of 20 or less on the Severity Alopecia Tool indicates 20% or less scalp hair loss or 80% or more of scalp coverage with hair.
Abbreviations: AA = alopecia areata; SALT = Severity of Alopecia Tool.
† Statistically significant vs placebo after adjustment for multiplicity of statistical comparisons.
*** p≤.001, ** p≤.01, * p≤.05 vs placebo without adjustment for multiple statistical comparisons.
Proportion of Patients Achieving Clinician Reported Outcome Measure for Eyebrows and Eyelashes at Week 36
At week 36, significantly more patients achieved ClinRO Eyebrow score of 0 or 1 with ≥2-point improvement from baseline in the
- baricitinib 4-mg treatment arm vs placebo arm in BRAVE-AA1 and BRAVE-AA2 (p≤.001 for both), and
- baricitinib 2-mg treatment arm vs placebo arm in BRAVE-AA1 (p≤.001; Proportion of Patients Achieving Clinician Reported Outcome Measure for Eyebrow Hair Loss of 0 or 1 Through Week 36 in BRAVE-AA1 and BRAVE-AA2).1
At week 36, significantly more patients achieved ClinRO Eyelash score of 0 or 1 with ≥2-point improvement from baseline in the baricitinib 4-mg treatment arm vs placebo arm in BRAVE-AA1 and BRAVE-AA2 (p≤.001 for both; Proportion of Patients Achieving Clinician Reported Outcome Measure for Eyelash Hair Loss of 0 or 1 Through Week 36 in BRAVE-AA1 and BRAVE-AA2).1
At week 36, in BRAVE-AA1, significantly more patients achieved a ClinRO Eyelash score of 0 or 1 with ≥2-point improvement from baseline in the baricitinib 2-mg treatment arm vs placebo arm when not controlling for multiple statistical comparisons (p≤.05).1
Figure Description: At week 36, in both BRAVE-AA1 and BRAVE-AA2, the proportion of patients achieving a score of 0 or 1 with 2 or more point improvement from baseline in the Clinician Reported Outcome Measure for Eyebrow Hair Loss was significantly higher in the baricitinib 4-mg group compared to placebo. In BRAVE-AA1, patients treated with 2 mg achieved significance for a score of 0 or 1 with a ≥2-point improvement from baseline compared with patients treated with placebo at week 36.
A score of 0 or 1 in the Clinician Reported Outcome Measure for Eyebrow Hair Loss indicates full coverage or minimal gaps in eyebrows. This analysis was only conducted in patients with a score ≥2 at baseline.
† Statistically significant vs placebo after adjustment for multiplicity of statistical comparisons.
*** p≤.001, ** p≤.01, * p≤.05 vs placebo without adjustment for multiple statistical comparisons.
Figure Description: At week 36, in both BRAVE-AA1 and BRAVE-AA2, the proportion of patients achieving a score of 0 or 1 with 2 or more point improvement from baseline in the Clinician Reported Outcome Measure for Eyelash Hair Loss was significantly higher in the baricitinib 4-mg group compared to placebo. At week 36, patients treated with baricitinib 2 mg did not achieve significance after multiplicity adjustment for a score of 0 or 1 with ≥2-point improvement from baseline.
A score of 0 or 1 in the Clinician Reported Outcome Measure for Eyelash Hair Loss indicates full coverage or minimal gaps in eyelashes. This analysis was conducted in patients with a score ≥2 at baseline.
† Statistically significant vs placebo after adjustment for multiplicity of statistical comparisons.
*** p≤.001, ** p≤.01, * p≤.05, vs placebo without adjustment for multiple statistical comparisons.
Safety Results
The safety population included all randomized patients who received ≥1 dose of study drug and who did not discontinue for the reason “Lost to Follow-up” at first postbaseline visit.1
Safety outcomes from the 36-week placebo-controlled period of BRAVE-AA1 and BRAVE-AA2 are summarized in Safety Outcomes During the 36-Week Placebo-Controlled Period of BRAVE-AA1 and BRAVE-AA2.
There were no reported deaths, venous thromboembolic events, opportunistic infections, or gastrointestinal perforations in either trial.1
In BRAVE-AA1, 1 myocardial infarction occurred in a patient with multiple risk factors and treated with baricitinib 2 mg. In BRAVE-AA2, 1 patient receiving placebo had prostate cancer, and 1 patient receiving baricitinib 4 mg had B-cell lymphoma.1
Number of Patients (%) |
BRAVE AA1 |
BRAVE AA2 |
||||
Placebo |
BARI 2 mg |
BARI 4 mg |
Placebo |
BARI 2 mg |
BARI 4 mg |
|
≥1 TEAE |
97 (51.3) |
93 (50.8) |
167 (59.6) |
97 (63.0) |
106 (68.4) |
154 (66.1) |
Severity of TEAE |
||||||
Mild |
49 (25.9) |
60 (32.8) |
106 (37.9) |
65 (42.2) |
60 (38.7) |
81 (34.8) |
Moderate |
41 (21.7) |
31 (16.9) |
54 (19.3) |
28 (18.2) |
42 (27.1) |
60 (25.8) |
Severe |
7 (3.7) |
2 (1.1) |
7 (2.5) |
4 (2.6) |
4 (2.6) |
13 (5.6) |
Serious AE |
3 (1.6) |
4 (2.2) |
6 (2.1) |
3 (1.9) |
4 (2.6) |
8 (3.4) |
Death |
0 |
0 |
0 |
0 |
0 |
0 |
AE leading to permanent treatment discontinuation |
2 (1.1) |
3 (1.6) |
5 (1.8) |
4 (2.6) |
4 (2.6) |
6 (2.6) |
AEs in ≥5% of patients in any group |
||||||
Upper respiratory tract infection |
10 (5.3) |
9 (4.9) |
21 (7.5) |
11 (7.1) |
12 (7.7) |
15 (6.4) |
Headache |
9 (4.8) |
8 (4.4) |
14 (5.0) |
10 (6.5) |
12 (7.7) |
21 (9.0) |
Nasopharyngitis |
12 (6.3) |
12 (6.6) |
21 (7.5) |
7 (4.5) |
2 (1.3) |
15 (6.4) |
Acne |
1 (0.5) |
10 (5.5) |
16 (5.7) |
3 (1.9) |
9 (5.8) |
11 (4.7) |
Urinary tract infection |
3 (1.6) |
2 (1.1) |
7 (2.5) |
2 (1.3) |
12 (7.7) |
11 (4.7) |
Blood CPK increased |
3 (1.6) |
3 (1.6) |
16 (5.7) |
2 (1.3) |
0 |
7 (3.0) |
Infectious AE |
||||||
≥1 treatment-emergent infection |
53 (28.0) |
46 (25.1) |
88 (31.4) |
45 (29.2) |
58 (37.4) |
69 (29.6) |
Serious infection |
0 |
0 |
0 |
0 |
2 (1.3) |
1 (0.4) |
Opportunistic infection |
0 |
0 |
0 |
0 |
0 |
0 |
Herpes zoster |
1 (0.5) |
1 (0.5) |
2 (0.7) |
1 (0.6) |
3 (1.9) |
3 (1.3) |
Herpes simplex |
4 (2.1) |
0 |
5 (1.8) |
8 (5.2) |
6 (3.9) |
2 (0.9) |
Tuberculosis |
0 |
0 |
0 |
0 |
0 |
0 |
Infections leading to permanent study treatment discontinuation |
0 |
0 |
0 |
0 |
1 (0.6) |
0 |
Abbreviations: AA = alopecia areata; AE = adverse event; BARI = baricitinib; CPK = creatine phosphokinase; TEAE = treatment-emergent adverse event.
aIn BRAVE-AA1, 1 patient randomized to BARI 2 mg and 1 patient randomized to BARI 4 mg, and in BRAVE-AA2, 2 patients randomized to placebo, 1 patient randomized to BARI 2 mg, and 1 patient randomized to BARI 4 mg are not included in safety analysis per safety population definition.
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1King B, Ohyama M, Kwon O, et al; BRAVE-AA Investigators. Two phase 3 trials of baricitinib for alopecia areata. N Engl J Med. 2022;386(18):1687-1699. https://doi.org/10.1056/nejmoa2110343
2Data on file, Eli Lilly and Company and/or one of its subsidiaries.
3Olsen EA, Hordinsky MK, Price VH, et al. Alopecia areata investigational assessment guidelines–part II. J Am Acad Dermatol. 2004;51(3):440-447. https://doi.org/10.1016/j.jaad.2003.09.032
4Wyrwich KW, Kitchen H, Knight S, et al. Development of clinician-reported outcome (ClinRO) and patient-reported outcome (PRO) measures for eyebrow, eyelash and nail assessment in alopecia areata. Am J Clin Dermatol. 2020;21(5):725-732. https://doi.org/10.1007/s40257-020-00545-9
5King B, Ohyama M, Kwon O, et al. Efficacy and safety of baricitinib in adults with alopecia areata: phase 3 results from two randomized controlled trials (BRAVE-AA1 and BRAVE-AA2). Abstract presented at: 30th Annual Meeting of the European Academy of Dermatology and Venereology (EADV Virtual); September 29-October 2, 2021.
Date of Last Review: May 13, 2025